1. Field of the Invention
This invention relates to a process for the manufacture of 5-methylpyrazine-2-carboxylic acid-4-oxide, its esters and conversion of the esters to pharmaceutically acceptable salts thereof.
2. Description of the Related Art
5-Methylpyrazinecarboxylic acid has been produced by several methods. Examplary methods include the following:
Patent Nos. JP62263164 and EP201934 disclose the preparation of 5-methylpyrazine-carboxylic acid using hydrogen peroxide and a tungstate or molybdate catalyst.
U.S. Pat. No. 4,051,245 discloses a process for the preparation of 5-methylpyrazine-carboxylic acid by the use of peracid oxidation of 5-methylpyrazinecarboxamide followed by basic hydrolysis of the amide oxide and pH adjustment.
The present invention is also partly directed to the preparation of 5-methylpyrazine-carboxylic acid-4-oxides that exhibit hypoglycemic and hypolipaemic activity. These products are used as such but can result in severe irritation of the gastrointestinal lining because of their low pH. The use of inorganic salts of these acids should alleviate this physiological side effect.
The present invention is also directed to the transformation of the 5-methylpyrazine-carboxylic acid-2-oxides to their inorganic salts.